title: Maternal smoking during pregnancy, fetal arterial resistance adaptations and cardiovascular function in childhood.
abstract: OBJECTIVE
  To unravel the mechanisms underlying the previously demonstrated associations between low birthweight and cardiovascular disease in adulthood, we examined whether maternal smoking during pregnancy leads to fetal arterial resistance adaptations, and subsequently to fetal growth retardation and changes in postnatal blood pressure and cardiac development.
  
  
  METHODS
  Prospective cohort study from early fetal life onwards.
  
  
  METHODS
  Academic hospital.
  
  
  METHODS
  Analyses were based on 1120 children aged 2 years.
  
  
  METHODS
  Maternal smoking during pregnancy [non-smoking, first trimester smoking, continued smoking (< 5 and ≥ 5 cigarettes/day)] was assessed by questionnaire.
  
  
  METHODS
  Third trimester placental and fetal arterial resistance indices and fetal growth were assessed by ultrasound and Doppler measurements. Postnatal blood pressure and cardiac structures (aortic root diameter, left atrial diameter, left ventricular mass) were measured at 2 years of age.
  
  
  RESULTS
  First trimester smoking was not associated with third trimester placental and fetal blood flow adaptations. Continued smoking of ≥ 5 cigarettes/day was associated with an increased resistance in uterine, umbilical and middle cerebral arteries, and with a decreased flow and diameter of the ascending aorta. Among mothers who continued to smoke, the third trimester estimated fetal weights and birthweights were most affected in children with the highest umbilical artery resistance. Fetal arterial resistance indices were also associated with aortic root diameter and left atrial diameter.
  
  
  CONCLUSIONS
  Fetal arterial resistance adaptations may be involved in the pathways leading from maternal smoking during pregnancy to low birthweight and cardiovascular developmental changes in childhood in the offspring.
authors.affiliation: The Generation R Study Group Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. j.geelhoed@erasmusmc.nl
authors.forename: J J M
authors.initials: JJ
authors.lastname: Geelhoed
authors.forename: H
authors.initials: H
authors.lastname: El Marroun
authors.forename: B O
authors.initials: BO
authors.lastname: Verburg
authors.forename: L
authors.initials: L
authors.lastname: van Osch-Gevers
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: A C
authors.initials: AC
authors.lastname: Huizink
authors.forename: H A
authors.initials: HA
authors.lastname: Moll
authors.forename: F C
authors.initials: FC
authors.lastname: Verhulst
authors.forename: W A
authors.initials: WA
authors.lastname: Helbing
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000151:congenital*; D015331:Cohort Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000503:physiopathology; D005318:Fetal Heart / Q000196:embryology; D005333:Fetus / Q000098:blood supply*; D006352:Heart Ventricles / Q000196:embryology; D006801:Humans; D007223:Infant; D020768:Middle Cerebral Artery; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking; D014655:Vascular Resistance / Q000502:physiology*